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Synergistic/antagonistic cytotoxic effects in mixtures of ionic liquids with doxorubicin or mitoxantrone

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Abstract An NMR spectroscopy study of ionic liquid/drug systems at a molecular level and a scanning electron microscopy study in the liquid phase at a nano-scale level were applied for… Click to show full abstract

Abstract An NMR spectroscopy study of ionic liquid/drug systems at a molecular level and a scanning electron microscopy study in the liquid phase at a nano-scale level were applied for the first time to study ionic preparations of well-known anticancer drugs. Cytotoxicity of binary mixtures of imidazolium ionic liquids with doxorubicin or mitoxantrone was studied in human colorectal adenocarcinoma CaCo-2 cells, and the evidence of synergism/antagonism was assessed. Of the ten drug-containing mixtures tested, four demonstrated significant synergistic or antagonistic cytotoxic effects. These mixtures revealed distinct micro-structured patterns, as shown by scanning electron microscopy, whereas nuclear magnetic resonance evidenced the formation of strong interactions between the drug and the ionic liquid in some of the mixtures. Notably, all the test substances induced the cell death via necrosis in the CaCo-2 cell line, thus revealing the dependence of the observed cytotoxic effects on the cell type. The observed synergistic effects suggested possible benefits of applying ionic liquids in drug formulations.

Keywords: cytotoxic effects; microscopy; doxorubicin mitoxantrone; liquids doxorubicin; ionic liquids; synergistic antagonistic

Journal Title: Journal of Molecular Liquids
Year Published: 2020

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